During the year of 2017-2018, we focused on studying the molecular mechanisms of malaria pathogenesis and signaling pathways using Plasmodium yoelii/mouse model. We have made good progresses in several projects: 1. We have finished functional verification of a parasite E3 ubiquitin ligase in regulating parasite growth and disease virulence. A manuscript was published by Nature Communications. Now we are studying the mechanism of how the changes in the E3 ubiquitin ligase affecting host immune responses. 2. We have also finished the study on mechanism of inflammatory responses during P. yoelii N67C infection. A paper has been published in Scientific Reports. We are now investigating the mechanism of anemia induced by infection of P. yoelii N67C parasite. 3. We have finished analyzing a large amount of microarray data to identify host immune pathways that are differentially activated or inhibited after infection with four different strains of P. yoelii parasites and 24 progeny of a genetic cross. Immune pathways inhibited after infections of these parasites have been identified. Removing the parasite-induced immune inhibition may improve vaccine development and disease treatment. A manuscript has been submitted to Scientific Reports. 4. We are finishing a project studying a gene called March1. We found that this gene can regulate host response to infections of multiple parasite strains. We are investigating the molecular mechanism of how this gene regulating host immune response. We are writing a manuscript for publication. 5. In a collaborative project with scientists in Xiamen University, China, we used a CRISPR/Cas9 method to study Plasmodium yoelii ApiAP2 genes. The results were published in mBio. Additionally, we also developed a transgenic parasite for efficient gene editing using CRISPR/Cas9. The results were published in Molecular and Biochemical Parasitology. 6. In collaboration with Dr. T.A Rouaults group at the National Institute of Child Health and Human Development, NIH, we finished a study on effects of erythrocytic ferroportin on intracellular iron accumulation, hemolysis and malaria risk. The results were published in Science. 7. We continued to work on other host molecules such as RTP4 and MMP3 that may affect host response to malaria infection.